Chapter 14:
Characteristics of Resistance and Susceptibility to Tuberculosis in Lurie’s Inbred Rabbits

Affiliations: 1: Center for Tuberculosis Research Departments of Environmental Health Sciences, Molecular Microbiology and Immunology, and Epidemiology, Bloomberg School of Public Health Department of Pathology, School of Medicine Johns Hopkins University, Baltimore, Maryland 21205

Lurie’s rabbits were inbred for either susceptibility or resistance to the progress of tuberculosis. When infected with virulent bovine-type tubercle bacilli, the susceptible rabbits developed a rapidly progressing, hematogenously spreading “childhood type” of tuberculosis, and the resistant rabbits developed a slowly progressing, cavitary, bronchial-spreading “adult type” of tuberculosis. In lesions produced by virulent bovine-type bacilli, by human-type bacilli, and by BCG, the same manifestations of genetic resistance to tuberculosis were evident histologically: mature epithelioid cells (now known as highly activated macrophages) were always more numerous in the lesions of resistant rabbits than in the lesions of susceptible rabbits, irrespective of the differences in virulence of the infecting bacillary strain. The genetic resistance of these rabbits resides in their ability to activate macrophages to control the growth of tubercle bacilli, both nonspecifically and immune-specifically. Crossbreeding showed that the genetic resistance to tuberculosis is multifactorial, with genes associated with resistance being dominant over susceptibility genes. The commercially available outbred New Zealand White rabbits seem almost as resistant as Lurie’s inbred resistant strain III rabbits. Thorbecke inbred rabbits were distinctly more susceptible than commercial outbred rabbits, but apparently not as susceptible as Lurie’s inbred C and FC rabbits. van Zutphen’s inbred rabbits (which are hypo- and hyper responsive to dietary cholesterol, respectively) have not been adequately studied for resistance to tuberculosis.

Ratios of individual rabbits from resistant strain III, susceptible strain C, and hybrids III × C, IIIC × C, and IIIC × III. The ratio is the number of inhaled human-type bacilli (H37Rv) required to generate one grossly visible primary tubercle; i.e., the ratio is the number of bacilli inhaled by each rabbit divided by the number of primary tubercles found in its lungs 5 weeks later. The mean ratios (by the Lurie method; see chapter 11) with their standard errors (and log10) are listed on the right.The original resistant and susceptible rabbit strains were III and C, respectively. The F1 hybrids were III × C, and the backcrosses were IIIC × C and IIIC × III, respectively. The resistance of the F1 generation backcrossed to resistant III rabbits was equal to that of the original III group (ratios of 620 ± 110 and 640 ± 170, respectively). However, the resistance of the F1 generation backcrossed to susceptible C rabbits was far greater than that of the original C group (ratios of 243 ± 51 and 48 ± 10, respectively). In other words, many of the factors controlling good resistance appeared to be dominant.This figure also shows the ratio as a log10 (and its arithmetic mean) for the rabbits in this experiment; each subsection represents one rabbit. For example, the IIIC × C contained 21 rabbits with ratios of 101.6 to 103.4, and the IIIC × III group contained 26 rabbits with ratios of 101.9to 103.7. Note that the resistance of the F1 generation seemed to be less variable than that of the other groups; i.e., it ranged over five rather than six 0.3 log10 increments (but this result may have been a chance phenomenon). The shaded boxes represent the rabbits shown in Fig. 1.Adapted from reference 14.Note the variation in tubercle counts among the individual rabbits.

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FIGURE 2

Ratios of individual rabbits from resistant strain III, susceptible strain C, and hybrids III × C, IIIC × C, and IIIC × III. The ratio is the number of inhaled human-type bacilli (H37Rv) required to generate one grossly visible primary tubercle; i.e., the ratio is the number of bacilli inhaled by each rabbit divided by the number of primary tubercles found in its lungs 5 weeks later. The mean ratios (by the Lurie method; see chapter 11) with their standard errors (and log10) are listed on the right.The original resistant and susceptible rabbit strains were III and C, respectively. The F1 hybrids were III × C, and the backcrosses were IIIC × C and IIIC × III, respectively. The resistance of the F1 generation backcrossed to resistant III rabbits was equal to that of the original III group (ratios of 620 ± 110 and 640 ± 170, respectively). However, the resistance of the F1 generation backcrossed to susceptible C rabbits was far greater than that of the original C group (ratios of 243 ± 51 and 48 ± 10, respectively). In other words, many of the factors controlling good resistance appeared to be dominant.This figure also shows the ratio as a log10 (and its arithmetic mean) for the rabbits in this experiment; each subsection represents one rabbit. For example, the IIIC × C contained 21 rabbits with ratios of 101.6 to 103.4, and the IIIC × III group contained 26 rabbits with ratios of 101.9to 103.7. Note that the resistance of the F1 generation seemed to be less variable than that of the other groups; i.e., it ranged over five rather than six 0.3 log10 increments (but this result may have been a chance phenomenon). The shaded boxes represent the rabbits shown in Fig. 1.Adapted from reference 14.Note the variation in tubercle counts among the individual rabbits.

3. Lurie,M. B.,, P.Zappasodi, and, C.Tickner.1955. On the nature of genetic resistance to tuberculosis in the light of the host-parasite relationships in natively resistant and susceptible rabbits.Am. Rev. Tuberc. Pulm. Dis.72:297–329.

26. Lurie,M. B.,, S.Abramson, and, A. G.Heppleston.1952. On the response of genetically resistant and susceptible rabbits to the quantitative inhalation of human-type tubercle bacilli and the nature of resistance to tuberculosis.J. Exp. Med.95:119–134.

29. Lurie,M. B.,, A. G.Heppleston,, S.Abramson, and, I. B.Swartz.1950. An evaluation of the method of quantitative airborne infection and its use in the study of the pathogenesis of tuberculosis.Am. Rev. Tuberc.61:765–797.

30. Lurie,M. B.,, P.Zappasodi,, R. S.Levy, and, R. G.Blaker.1959. On the role of the thyroid in native resistance to tuberculosis. I. The effect of hyperthyroidism.Am. Rev. Respir. Dis.79:152–179.

33. Lurie,M. B.1944. Experimental epidemiology of tuberculosis: hereditary resistance to attack by tuberculosis and to the ensuing disease and the effect of the concentration of tubercle bacilli upon these two phases of resistance.J. Exp. Med.79:573–589.

Tables

Characteristics of Resistance and Susceptibility to Tuberculosis in Lurie’s Inbred Rabbits

Relative resistance of Lurie’s inbred rabbit strains, determined by their survival after a standard intracutaneous inoculation of virulent bovine-type tubercle bacilli (Ravenel), by their response to the quantitative inhalation of human-type tubercle bacilli (H37Rv), or by both

TABLE 1

Relative resistance of Lurie’s inbred rabbit strains, determined by their survival after a standard intracutaneous inoculation of virulent bovine-type tubercle bacilli (Ravenel), by their response to the quantitative inhalation of human-type tubercle bacilli (H37Rv), or by both